Adipose mesenchymal stem cells protect chondrocytes from degeneration associated with osteoarthritis

Abstract

Our work aimed at evaluating the role of adipose stem cells (ASC) on chondrocytes from osteoarthritic (OA) patients and identifying the mediators involved. We used primary chondrocytes, ASCs from different sources and bone marrow mesenchymal stromal cells (MSC) from OA donors. ASCs or MSCs were co-cultured with chondrocytes in a minimal medium and using cell culture inserts. Under these conditions, ASCs did not affect the proliferation of chondrocytes but significantly decreased camptothecin-induced apoptosis. Both MSCs and ASCs from different sources allowed chondrocytes in the cocultures maintaining a stable expression of markers specific for a mature phenotype, while expression of hypertrophic and fibrotic markers was decreased. A number of factors known to regulate the chondrocyte phenotype (IL-1β, IL-1RA, TNF-α) and matrix remodeling (TIMP-1 and -2, MMP-1 and -9, TSP-1) were not affected. However, a significant decrease of TGF-β1 secretion by chondrocytes and induction of HGF secretion by ASCs was observed. Addition of a neutralizing anti-HGF antibody reversed the anti-fibrotic effect of ASCs whereas hypertrophic markers were not modulated. In summary, ASCs are an interesting source of stem cells for efficiently reducing hypertrophy and dedifferentiation of chondrocytes, at least partly via the secretion of HGF. This supports the interest of using these cells in therapies for osteo-articular diseases.

AB0062 Ex vivo back-translation of fostamatinib's effect on joint ecm turnover shows significant effect on bone but no effect on the synovium

“…Background: Osteoarthritis (OA) is the most common joint disease and the major cause of pain and disability in the aging population [1]. Adipose stromal cells (ASC) are promising candidate for cell therapy in OA, because they have immunomodulatory, trophic and differentiation capacities [2,3]. Synovial inflammation is accepted as important OA feature for the symptoms and disease progression [4].…”

Adipose derived stem cells for regenerative therapy in osteoarticular diseases

“…Recently, Maumus et al showed that ASCs induced no changes on the proliferation of chondrocytes but decreased expression of hypertrophic and fibroblastic markers on OA chondrocytes. Hepatocyte growth factor seems a key mediator of this process [38].…”

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“…Hence, it is important to remember the key role played by cytokines and growth factors in osteophyte formation, the elevation of TGF-β1 41 and HGF levels in OA cartilage 42,43 , and elevated messenger RNA (mRNA) and protein levels of both TGF-β1 41,44 and HGF 42 in OA osteoblasts. MSC isolated from adipose tissue secrete HGF that can decrease TGF-β1 production in co-cultures with chondrocytes, indicating another potential crosstalk between different joint tissues 45 . Osteophyte formation may be considered a repair response to stabilize the damaged joints, and it requires the local recruitment of speci ic MSC 46 .…”